The prevalence of treated end-stage renal disease in American Indians (AIs) is 3.5 times higher than in White Americans, while the mean age of onset of end-stage renal disease is 6 years younger than in Whites. Despite similar referral rates for kidney transplantation, AIs are less likely than Whites to be placed on the transplant waiting list or to receive a transplant. In 2009, 7,682 AIs were on dialysis, but only 876 were on the waiting list. Still worse, only 20 living kidney donors nationwide were AI in 2011. These findings reflect complex causal factors, especially for rural AIs, including long distances between reservations and transplant centers; difficulties completing pre-transplant evaluations; a shortage of matching kidneys; concerns about the spiritual implications of transplantation; and perceived discrimination. In 2007, NIDDK funded 6 academic centers, including our own, to test ways to increase organ donation in minorities. We partnered with 5 tribal colleges for a mixed-methods project to understand beliefs about and barriers to kidney donation among AIs. Our qualitative work revealed that AIs are willing to donate organs to family members and other Native recipients. Our survey of 1,231 community members at local tribal events found that the decision to become an organ donor was most strongly influenced by talking with family or project staff and by watching a personalized digital story about organ donation. At these events, 15% of respondents registered to become donors. These findings inform our strategy to conduct a multi-level intervention to increase kidney donation at 3 rural sites: the Lummi Nation and adjacent communities in Washington, and the Fort Peck Tribes and Blackfeet Nation in Montana. Our overarching goal is to increase living kidney donation. We leverage research conducted under RFA DK- 06-016 by adapting Dr. James Rodrigue's House Calls program, Dr. Prabhakar Baliga's patient navigation project, and Dr. L. Ebony Boulware's educational materials. Our specific aims are to: 1) increase living donor kidney transplants by using new media and by adapting existing educational materials and a successful in- home transplantation education program for use in AI communities; 2) improve completion of transplantation evaluations through patient navigation; 3) encourage deceased donation by soliciting donor registration at community events and providing culturally tailored materials to LifeCenter Northwest donation facilitators at critical care hospitals; and 4) survey AI dialysis patients in te Northwest Renal Network to augment our knowledge of kidney donation and transplantation in AIs. This innovative project capitalizes on NIDDK's investments in minority organ donation and our relationships with tribal communities. Given the striking prevalence of diabetes, the rapid increase in chronic and end-stage renal disease, and the frequency of rural residence among AIs, we need more knowledge of the factors that influence decisions to donate kidneys, as well as new strategies to translate this knowledge into culturally acceptable approaches to increasing kidney donation and transplantation. PUBLIC HEALTH RELEVANCE: Rates of chronic and end-stage kidney disease are disproportionately high among American Indians, while rates of kidney donation and transplantation are the lowest of any racial or ethnic group in the U.S. New strategies are urgently needed to increase kidney donation and transplantation to improve the quality of life of this dramatically underserved population. Building on our previous work on kidney donation in tribal communities, and leveraging successful efforts by other researchers in racial minority groups, the proposed multi-level, multi-site study will return findings with immediate clinical and public health implications for healthcare facilities that serve American Indians.